Intra-Articular Use of Hyaluronic Acid in the Treatment of Knee Osteoarthritis

PICHON RIVIERE, A.; AUGUSTOVSKI, F.; GARCIA MARTI, S.; ALCARAZ, A.; GLUJOVSKY, D.; LOPEZ, A.; REY-ARES, L.; BARDACH, A.; CIAPPONI, A

Documento de Evaluación de tecnologías Sanitarias

IECS

Año: 2013 p. 1 - 30

1668-2793

Knee osteoarthritis (OA) is observed in approximately 6% of the people over 30 years old and up to 40% of those 70 years old, showing focal damage in the joint cartilage, causing pain and movement disorders.The available non-pharmacological treatments include educational and exercise programs, among others. When necessary, they may be associated to pharmacological treatments, such as simple analgesics and non-steroidal anti-inflammatory drugs (NSAIDs). Intra-articular corticosteroids are used as short-term therapy, for symptomatic pain relief.When these treatments are not enough, intra-articular hyaluronic acid (HA) use is proposed.TechnologyHyaluronic acid is part of the synovial fluid and the cartilage. Its visco-elastic density allows blow impacts to be absorbed. Viscous supplementation implies using HA in the intra-articular space, usually once a week for 3-5 weeks. On occasions, several cycles are proposed.The U.S. Food and Drug Administration (FDA) approved the use of HA for patients with knee OA who have not responded to non-pharmacological treatments and simple analgesics. Argentina?s regulatory agency, ANMAT, authorized its use in 2010.PurposeTo assess the available evidence on the efficacy, safety and coverage policy related aspects regarding the use of intra-articular hyaluronic acid in patients with knee osteoarthritis.MethodsA bibliographic search was carried out on the main databases: DARE, NHS EED, on Internet general search engines, in health technology evaluation agencies and health sponsors. Priority was given to the inclusion of systematic reviews (SR); controlled, randomized clinical trials (RCTs); health technology assessments (HTA) and economic evaluations; clinical practice guidelines (CPG) and coverage policies of other health systems.ResultsThree SR, two CPG, three HTA and four coverage policies were found.In one systematic review published in 2012, similarly to one Cochrane review of 2009, it was found that when comparing HA with placebo, the HA group had improvements regarding pain relief (between 28% and 54% improvement) and function (between 9% and 32% improvement), with 5 and 26 weeks follow-up. Similar differences were found favoring HA when compared with NSAIDs, and this benefit was found for a longer term when comparing HA with intra-articular corticosteroids. These latter data is also mentioned in another systematic review published in 2009, HA use being beneficial against corticosteroids at 8, 12 and 26 weeks.The American College of Rheumatology, similar to the Osteoarthritis Research Society International, published in 2012 that they recommend HA for those patients not responding to initial treatment (non-pharmacological and pharmacological measures).Two HTAs published in the United States in 2010 and 2011 consider there is consistent evidence on HA benefits for pain relief an mobility, although one mentions this benefit would be of little clinical significance. Compared with intra-articular corticosteroids, there is poor quality evidence on longer-term benefit.One HTA published in 2011 in Spain does not recommend HA use for Grade 1-2 knee OA as a general rule.The CPGs published in 2008 by the British agency, NICE, recommends not using HA in osteoarthritis (based on a cost-effectiveness analysis). The Canadian Agency, CADTH, published in 2006 one document which mentions that there is evidence of modest improvements in terms of pain relief and mobility at short-term. One Australian agency, similar to a U.S. one considers HA could be used when non-pharmacologic treatments, analgesics or NSAIDs have not been successful and moderate or severe symptoms persist.The cost of one cycle with three HA administrations is about AR$4,000 (Argentine Pesos, March 2013), equivalent to about USD 775 (U.S. Dollars).ConclusionsThe evidence found is of high methodological quality. The studies found show that intra-articular hyaluronic acid, when used in patients with knee osteoarthritis who have not responded to non-pharmacological treatments and pharmacological treatments with simple analgesics, slightly reduces pain and improves mobility compared with placebo, analgesics or intra-articular corticosteroids, in the 3-6 month evaluated period.There is still not enough information published stating if repeated use is better than a single-dose, or if the benefit showed persists at a longer term. Also, there was no evidence found on the effectiveness, as a single or repeated doses, in relation to stopping osteoarthritis progression, or if it reduces the likelihood of requiring joint replacement.Most Clinical Practice Guidelines and Health Sponsors consulted agree to cover HA for knee OA which has not responded to non-pharmacological and pharmacological treatments. They do not mention if its use is covered as single or repeated doses.More studies assessing the evolution of single and repeated doses at a longer term are needed to reach better conclusions.